Many voice disorders feature structural vocal fold asymmetries, such as a difference in vocal fold left-right position, height, length or stiffness (e.g. unilateral vocal fold paresis and paralysis, vocal fold polyps, vocal fold scarring, etc.). When the asymmetries are mild, present therapies are effective for most patients. However, when the asymmetries are significant or multiple, outcomes are more uncertain. Such patients represent an important health problem, because the severity of their voice disorder significantly affects them physically, psychologically and economically. In any field, clinical decision-making about intervention strategies depends on a combination of clinical outcome data and the understanding of underlying mechanisms. For these patients, both because clinical data are limited and because the problems are so complex, scientific understanding of how structural asymmetries affect vocal fold vibration and voice production is particularly important. It has long been acknowledged that vortices, or areas of rotational motion, occur in the laryngeal airflow, but their relevance has not been clear. Using well-established experimental and theoretical approaches from engineering, we have found evidence that vortical structures are particularly relevant in cases of vocal fold asymmetries. In this previous work, supported by a K-8 grant to the principal investigator, our team has measured velocity fields of phonatory airflow in excised canine larynges, with particular interest in quantifying vortices. Our completed studies (Khosla et al., 2007, 2008a and 2009;Murugappan, Khosla et al., 2009) provide a supportive foundation to the overarching hypothesis of this application, which is: glottal airflow contains certain vortical structures that significantly contribute to the acoustics;and that in certain laryngeal pathologies, these vortical structures are reduced or eliminated. It is the modification and/or suppression of these vortices that contribute to abnormal voice production. Treatments that most effectively restore specific vortices will have the best voice outcomes. In order to test the central hypothesis, we propose to organize our study around the following specific aims. Excised canine and human larynges will be used for all aims. Specific Aim 1 - Using computational and validated excised hemilarynx models, characterize the effects of vortices and tissue elasticity on vocal fold vibration and acoustics. Specific Aim 2 - Vortices, tissue elasticity, vocal fold vibration and acoustics will be measured as functions of different, clinically relevant structural asymmetries. Specific Aim 3 -The change in structural asymmetries, vibratory asymmetries and acoustics will be measured after a single procedure or a combination of the following procedures for unilateral vocal fold paralysis: Thyroplasty Type 1, Adduction Arytenopexy and Cricothyroid Subluxation. PUBLIC HEALTH RELEVANCE: The results of the proposed research will provide an approach to clinically study patients with vocal fold asymmetry. Looking forward, the study of phonation at this resolution will synergize well with advancing technologies in laryngeal imaging, such as videokymography (Svec et al) and high speed videography (Delyiski) as available clinical technology allows for more precise and reliable identification of asymmetries. The findings will have far reaching impact in laryngology as the results may be applicable to other conditions in the larynx that result in vocal fold asymmetries , such as vocal fold scarring and vocal fold sulcus. These results will have positive impact, since the new knowledge will result in improved diagnostic and clinical techniques that could not be otherwise developed.